Identification of cortical interneuron cell markers in mouse embryos based on machine learning analysis of single-cell transcriptomics

Abstract

Mammalian cortical interneurons (CINs) could be classified into more than two dozen cell types that possess diverse electrophysiological and molecular characteristics, and participate in various essential biological processes in the human neural system. However, the mechanism to generate diversity in CINs remains controversial. This study aims to predict CIN diversity in mouse embryo by using single-cell transcriptomics and the machine learning methods. Data of 2,669 single-cell transcriptome sequencing results are employed. The 2,669 cells are classified into three categories, caudal ganglionic eminence (CGE) cells, dorsal medial ganglionic eminence (dMGE) cells, and ventral medial ganglionic eminence (vMGE) cells, corresponding to the three regions in the mouse subpallium where the cells are collected. Such transcriptomic profiles were first analyzed by the minimum redundancy and maximum relevance method. A feature list was obtained, which was further fed into the incremental feature selection, incorporating two classification algorithms (random forest and repeated incremental pruning to produce error reduction), to extract key genes and construct powerful classifiers and classification rules. The optimal classifier could achieve an MCC of 0.725, and category-specified prediction accuracies of 0.958, 0.760, and 0.737 for the CGE, dMGE, and vMGE cells, respectively. The related genes and rules may provide helpful information for deepening the understanding of CIN diversity.